Perioperative Nivolumab Improves EFS in Resectable NSCLC

Neoadjuvant nivolumab plus chemotherapy, as demonstrated in the CheckMate 816 trial, significantly improves event-free survival (EFS) and pathological complete response (pCR) in patients with resectable non-small cell lung cancer (NSCLC).

This regimen is currently the only approved neoadjuvant immunotherapy-containing treatment for this condition. The CheckMate 77T trial built upon this standard of care (SOC) by demonstrating clinically meaningful improvements in EFS and pCR when comparing perioperative nivolumab to a placebo.

Patrick Forde and the team spearheaded a study that aimed to evaluate the contribution of the adjuvant phase of the perioperative nivolumab treatment regimen using individual patient-level data from the CheckMate 77T and CheckMate 816 trials.

This analysis included patients from CheckMate 77T who received neoadjuvant nivolumab plus chemotherapy, followed by definitive surgery and at least one dose of adjuvant nivolumab.
Patients were compared to patients from CheckMate 816 who received neoadjuvant nivolumab plus chemotherapy followed by definitive surgery. The database lock dates were April 26, 2024, for CheckMate 77T and October 20, 2021, for CheckMate 816. These dates were chosen to provide similar median follow-up times of 33.3 and 29.5 months, respectively.

Inverse probability of treatment weighting (IPTW) was used to adjust for potential cross-trial imbalances in baseline covariates. This was done using propensity score weights to determine the stabilised average treatment effect for the treated (ATT) and the stabilised average treatment effect (ATE).

Assessments included EFS landmarked from the time of definitive surgery in both the weighted and unweighted analysis populations, and in subgroups (unweighted) defined by PD-L1 expression, clinical stage, and pCR status. Safety was also assessed.

After weighting, baseline characteristics were balanced between the perioperative nivolumab (N=139) and neoadjuvant nivolumab (N=147) analysis populations. Perioperative nivolumab demonstrated an EFS benefit from the time of surgery compared to neoadjuvant nivolumab (HR [95% CI]: unweighted, 0.59 [0.38-0.92]; weighted [ATT], 0.56 [0.35-0.90]; weighted [ATE], 0.61 [0.39-0.97]). This landmark EFS benefit with perioperative versus neoadjuvant nivolumab was also observed in patients with PD-L1 <1% or ≥1% and across clinical stages (IB/II or III).

Furthermore, landmark EFS favoured perioperative nivolumab in patients both with and without pCR. Grade 3-4 treatment-related adverse events occurred in 27% of patients receiving perioperative nivolumab and 35% of those receiving neoadjuvant nivolumab.

This landmark IPTW EFS analysis indicated that perioperative nivolumab improves EFS compared to neoadjuvant nivolumab in patients with resectable NSCLC. This includes patients with PD-L1 <1% or those without pCR.

While the limitations of propensity score weighted analysis mean that the results should be interpreted with caution, this remains the first individual patient-level data cross-trial analysis of phase 3, international, randomized trials to assess the contribution of the adjuvant phase of a perioperative immunotherapy-based regimen.

These findings further support perioperative nivolumab as a treatment option for patients with resectable NSCLC.

The trial was sponsored by Bristol-Myers Squibb.

Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/3196

Clinical Trials: https://clinicaltrials.gov/study/NCT04025879
https://clinicaltrials.gov/study/NCT02998528

Forde PM, Peters S, Donington J, et al. (2024). “Perioperative vs Neoadjuvant Nivolumab for Resectable NSCLC: Patient-Level Data Analysis of CheckMate 77T vs CheckMate 816.” Presented at: World Conference on Lung Cancer (WCLC); September 8, 2024; Singapore.